The conformational analysis of heterocyclic systems. Part VIII. Kinetics of quaternisation of N-alkylpiperidines and N-alkylpiperazines in acetonitrile

Abstract

Rates of reaction are reported for series of 1-alkyl-4-phenylpiperidines and 1-alkyl-4-t-butylpiperazines with methyl iodide in acetonitrile solution at –35 to +40°. The results are compared with rates for quinazolines (from the literature) and 2-methyl-2-aza-adamantane and N-methyltropane. The proportions of the isomeric quaternary salts formed have been determined by n.m.r. spectroscopy. It is concluded that 1-alkyl-4-phenylpiperidines and 1-alkyl-4-t-butylpiperazines undergo predominant equatorial alkylation except in the case of the N-t-butyl derivatives.